Given the enormous number of HIV-infected people worldwide, most epidemiologists agree that a vaccine is the only practical solution to stemming the AIDS epidemic. Although a number of different strategies could be utilized, no strategy has yet been proven to elicit a better immune response than one based on the envelope glycoprotein, gp120. These vaccines exhibit almost all the technical characteristics of an ideal vaccine. They elicit neutralizing antibodies effective against both macrophage tropic and T cell tropic strains of HIV-1. They are capable of stimulating antibodies reactive with the common polymorphisms, appear safe, and are affordable for worldwide distribution. Our goal is to generate H1V subtype C gp120 protein antigens to use in either a multivalent vaccine or as a component of a prime-boost regimen. Virus will be collected and cloned and their respective gp120 genes will be sequenced. The sequence analysis will be used to identify the polymorphisms within the neutralizing epitopes. The bioinformatic results will guide the selection of gp120 molecules that will be transiently expressed and purified. A high throughput neutralization assay will be developed in order to examine a large number of antigen combinations in a timely manner. PROPOSED COMMERCIAL APPLICATION: The potential commercial application of this research is a subtype C HIV vaccine.